Receptors Linked to Hydrolysis of Choline Phospholipids: the Role of Phospholipase D in a Putative Mechanism of Signal Transduction

1990 ◽  
pp. 49-76 ◽  
Author(s):  
Konrad Löffelholz
Keyword(s):  
Signal Transduction ◽  
Phospholipase D ◽  
Hydrolysis Of ◽  
Putative Mechanism

scholarly journals Organization and alternative splicing of the murine phospholipase D2 gene

1998 ◽  
Vol 331 (3) ◽  
pp. 845-851 ◽  
Author(s):  
Olga E. REDINA ◽  
Michael A. FROHMAN
Keyword(s):  
Signal Transduction ◽  
Alternative Splicing ◽  
Phospholipase D ◽  
Untranslated Region ◽  
Genomic Organization ◽  
Proximal Promoter ◽  
Promoter Sequences ◽  
Phospholipase D2 ◽  
Alternatively Spliced ◽  
Hydrolysis Of

Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine, generating phosphatidic acid and choline. Mammalian PLD activity derives from a family of membrane-associated enzymes that are activated by a wide variety of signal transduction events. cDNA species encoding human, mouse and rat PLD1 and PLD2 have recently been reported. In this study we undertook to determine the organization of the mouse PLD2 gene. We report that the gene spans 17.1 kb and contains 25 exons. Mouse PLD2 is notable for a relatively GC-rich and large 5´ untranslated region. Proximal promoter sequences upstream of the first exon contain several consensus SP1 sequences (GGGCGG) but lack TATA and CAAT boxes. Finally, alternatively spliced cDNA species identified for PLD1 and PLD2 are discussed in the context of the PLD2 genomic organization.

Phospholipase D Activity Is Essential for PKC-Mediated Phosphatidylserine Exposure.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1715-1715
Author(s):  
Kitty DeJong ◽  
Shahrzad A. Rahbar ◽  
Frans A. Kuypers
Keyword(s):  
Signal Transduction ◽  
Phospholipase D ◽  
Feedback Inhibition ◽  
Annexin V ◽  
Lipid Mediator ◽  
Primary Alcohols ◽  
Subsequent Formation ◽  
Sickle Cells ◽  
Dependent Inhibition

Abstract The adverse effects of red blood cells (RBC) that expose phosphatidylserine (PS) in the sickle cell circulation are well recognized. However, the mechanism that underlies the formation of these cells is not well understood. We have shown previously that activation of protein kinase C (PKC) using phorbol myristate acetate (PMA) stimulates RBC to expose PS on a subset of cells. This process was dependent on Ca2+-influx induced by this stimulation. PKC inhibitors were shown to counteract this process and also reduce PS exposure induced by high levels of intracellular Ca2+. Furthermore, PIP2 administered to the RBC similarly induces PS exposure. Because both PKC and PIP2 can stimulate phospholipase D (PLD), we investigated the role of PLD in signal transduction initiated phospholipid scrambling. PLD cleaves phospholipids to produce phosphatidic acid (PA), which can be further metabolized to lysophosphatidic acid, an important lipid mediator, or to diacylglycerol (DAG), itself a PKC activator. In presence of primary alcohols such as ethanol or 1-butanol, PLD generates phosphatidylethanol or phosphatidylbutanol, respectively. Using annexin V, we measured the fraction of PS-exposing cells after treatment of RBC with PMA in presence of these primary alcohols. Treatment with 1% ethanol as well as 0.2% 1-butanol (at 0.4% hematocrit) completely abolished the generation of PS exposure in PMA-treated cells, indicating that the formation of PA by PLD was essential for scrambling. Anandamides are structural analogues of arachidonoyl ethanolamide, an endocannabinoid. Since these structures provide feedback inhibition of the PLD-isoform that produces these compounds in the brain and were found effective on plant PLD isoforms, we evaluated their effect on PLD-mediated PS scrambling in our assay. Short-chain lauroyl ethanolamide as well as arachidonoyl ethanolamide itself induced concentration-dependent inhibition of PMA-induced PS exposure. This suggests that these compounds indeed inhibit the isoforms of PLD present in the RBC, and confirms the importance of PLD activity for PKC-mediated PS exposure. Furthermore we evaluated the effect of propranolol, which inhibits phosphatidate phosphatase, the enzyme that converts PA to DAG. PMA-induced PS exposure was more than 80% inhibited by propranolol, indicating that the conversion of DAG from PLD-generated PA is essential for PKC-mediated PS exposure. PLD inhibitors did not inhibit Ca2+-induced scrambling initiated with Ca-ionophore, indicating that loading RBC with high levels of intracellular Ca2+ can override the requirement for PLD activation, possibly because DAG is formed through direct activation of phospholipase C. These results show that PLD activation is essential for PMA-induced Ca-influx and PS exposure, and that the subsequent formation of DAG from PA is a critical step in this process. Altered Ca2+ homeostasis, increased PA generation and increased PKC activation are observed in sickle RBC. Our data indicate that activation of signal transduction pathways plays an important role in generating PS exposure in sickle cells.

scholarly journals An Explanation for the Adiponectin Paradox

2021 ◽  
Vol 14 (12) ◽  
pp. 1266
Author(s):  
Hans O. Kalkman
Keyword(s):  
Insulin Resistance ◽  
Signal Transduction ◽  
Insulin Sensitivity ◽  
Phospholipase D ◽  
Functional Consequence ◽  
Glycosyl Phosphatidylinositol ◽  
Paradoxical Situation ◽  
Hydrolysis Of ◽  
Circulating Levels ◽  
Sensitivity Functional

The adipokine adiponectin improves insulin sensitivity. Functional signal transduction of adiponectin requires at least one of the receptors AdipoR1 or AdipoR2, but additionally the glycosyl phosphatidylinositol-anchored molecule, T-cadherin. Overnutrition causes a reduction in adiponectin synthesis and an increase in the circulating levels of the enzyme glycosyl phosphatidylinositol-phospholipase D (GPI-PLD). GPI-PLD promotes the hydrolysis of T-cadherin. The functional consequence of T-cadherin hydrolysis is a reduction in adiponectin sequestration by responsive tissues, an augmentation of adiponectin levels in circulation and a (further) reduction in signal transduction. This process creates the paradoxical situation that adiponectin levels are augmented, whereas the adiponectin signal transduction and insulin sensitivity remain strongly impaired. Although both hypoadiponectinemia and hyperadiponectinemia reflect a situation of insulin resistance, the treatments are likely to be different.

scholarly journals SPO14 Separation-of-Function Mutations Define Unique Roles for Phospholipase D in Secretion and Cellular Differentiation in Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 158 (4) ◽  
pp. 1431-1444 ◽  
Author(s):  
Simon A Rudge ◽  
Trevor R Pettitt ◽  
Chun Zhou ◽  
Michael J O Wakelam ◽  
JoAnne Engebrecht
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Cellular Differentiation ◽  
Physiological Processes ◽  
Catalytically Active ◽  
Hydrolysis Of ◽  
Secretory Apparatus

Abstract In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene, catalyzes the hydrolysis of phosphatidylcholine, producing choline and phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis and is required for Golgi function when the normal secretory apparatus is perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14 that support Sec14-independent secretion but not sporulation. Identification of these separation-of-function alleles indicates that the role of PLD in these two physiological processes is distinct. Analyses of the mutants reveal that the corresponding proteins are stable, phosphorylated, catalytically active in vitro, and can localize properly within the cell during meiosis. Surprisingly, the separation-of-function mutations map to the conserved catalytic region of the PLD protein. Choline and phosphatidic acid molecular species profiles during Sec14-independent secretion and meiosis reveal that while strains harboring one of these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent secretion, they fail to do so during sporulation or normal vegetative growth. These results demonstrate that Spo14 PLD catalytic activity and cellular function can be differentially regulated at the level of phosphatidylcholine hydrolysis.

Magnesium and Hearing

2003 ◽  
Vol 14 (04) ◽  
pp. 202-212 ◽  
Author(s):  
Michael J. Cevette ◽  
Jürgen Vormann ◽  
Kay Franz
Keyword(s):  
Hair Cells ◽  
Auditory Nerve ◽  
Mg Deficiency ◽  
Noise Damage ◽  
Susceptibility To Noise ◽  
Major Progress ◽  
A Current ◽  
Putative Mechanism ◽  
Increased Susceptibility

The last several decades have revealed clinical and experimental data regarding the importance of magnesium (Mg) in hearing. Increased susceptibility to noise damage, ototoxicity, and auditory hyperexcitibility are linked to states of Mg deficiency. Evidence for these processes has come slowly and direct effects have remained elusive because plasma Mg levels do not always correlate with its deficiency. Despite the major progress in the understanding of cochlear mechanical and auditory nerve function, the neurochemical and pharmacologic role of Mg is not clear. The putative mechanism suggests that Mg deficiency may contribute to a metabolic cellular cascade of events. Mg deficiency leads to an increased permeability of the calcium channel in the hair cells with a consequent over influx of calcium, an increased release of glutamate via exocytosis, and over stimulation of NMDA receptors on the auditory nerve. This paper provides a current overview of relevant Mg metabolism and deficiency and its influence on hearing.

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